Neural populations within macaque early vestibular pathways are adapted to encode natural self-motion.

How the activities of large neural populations are integrated in the brain to ensure accurate perception and behavior remains a central problem in systems neuroscience. Here, we investigated population coding of naturalistic self-motion by neurons within early vestibular pathways in rhesus macaques (Macacca mulatta). While vestibular neurons displayed similar dynamic tuning to self-motion, inspection of their spike trains revealed significant heterogeneity. Further analysis revealed that, during natural but not artificial stimulation, heterogeneity resulted primarily from variability across neurons as opposed to trial-to-trial variability. Interestingly, vestibular neurons displayed different correlation structures during naturalistic and artificial self-motion. Specifically, while correlations due to the stimulus (i.e., signal correlations) did not differ, correlations between the trial-to-trial variabilities of neural responses (i.e., noise correlations) were instead significantly positive during naturalistic but not artificial stimulation. Using computational modeling, we show that positive noise correlations during naturalistic stimulation benefits information transmission by heterogeneous vestibular neural populations. Taken together, our results provide evidence that neurons within early vestibular pathways are adapted to the statistics of natural self-motion stimuli at the population level. We suggest that similar adaptations will be found in other systems and species.

The neural basis for violations of Weber's law in self-motion perception.

A prevailing view is that Weber's law constitutes a fundamental principle of perception. This widely accepted psychophysical law states that the minimal change in a given stimulus that can be perceived increases proportionally with amplitude and has been observed across systems and species in hundreds of studies. Importantly, however, Weber's law is actually an oversimplification. Notably, there exist violations of Weber's law that have been consistently observed across sensory modalities. Specifically, perceptual performance is better than that predicted from Weber's law for the higher stimulus amplitudes commonly found in natural sensory stimuli. To date, the neural mechanisms mediating such violations of Weber's law in the form of improved perceptual performance remain unknown. Here, we recorded from vestibular thalamocortical neurons in rhesus monkeys during self-motion stimulation. Strikingly, we found that neural discrimination thresholds initially increased but saturated for higher stimulus amplitudes, thereby causing the improved neural discrimination performance required to explain perception. Theory predicts that stimulus-dependent neural variability and/or response nonlinearities will determine discrimination threshold values. Using computational methods, we thus investigated the mechanisms mediating this improved performance. We found that the structure of neural variability, which initially increased but saturated for higher amplitudes, caused improved discrimination performance rather than response nonlinearities. Taken together, our results reveal the neural basis for violations of Weber's law and further provide insight as to how variability contributes to the adaptive encoding of natural stimuli with continually varying statistics.

Coding of envelopes by correlated but not single-neuron activity requires neural variability.

Understanding how the brain processes sensory information is often complicated by the fact that neurons exhibit trial-to-trial variability in their responses to stimuli. Indeed, the role of variability in sensory coding is still highly debated. Here, we examined how variability influences neural responses to naturalistic stimuli consisting of a fast time-varying waveform (i.e., carrier or first order) whose amplitude (i.e., envelope or second order) varies more slowly. Recordings were made from fish electrosensory and monkey vestibular sensory neurons. In both systems, we show that correlated but not single-neuron activity can provide detailed information about second-order stimulus features. Using a simple mathematical model, we made the strong prediction that such correlation-based coding of envelopes requires neural variability. Strikingly, the performance of correlated activity at predicting the envelope was similarly optimally tuned to a nonzero level of variability in both systems, thereby confirming this prediction. Finally, we show that second-order sensory information can only be decoded if one takes into account joint statistics when combining neural activities. Our results thus show that correlated but not single-neural activity can transmit information about the envelope, that such transmission requires neural variability, and that this information can be decoded. We suggest that envelope coding by correlated activity is a general feature of sensory processing that will be found across species and systems.

The statistics of the vestibular input experienced during natural self-motion differ between rodents and primates.

KEY POINTS: In order to understand how the brain's coding strategies are adapted to the statistics of the sensory stimuli experienced during everyday life, the use of animal models is essential. Mice and non-human primates have become common models for furthering our knowledge of the neuronal coding of natural stimuli, but differences in their natural environments and behavioural repertoire may impact optimal coding strategies. Here we investigated the structure and statistics of the vestibular input experienced by mice versus non-human primates during natural behaviours, and found important differences. Our data establish that the structure and statistics of natural signals in non-human primates more closely resemble those observed previously in humans, suggesting similar coding strategies for incoming vestibular input. These results help us understand how the effects of active sensing and biomechanics will differentially shape the statistics of vestibular stimuli across species, and have important implications for sensory coding in other systems. ABSTRACT: It is widely believed that sensory systems are adapted to the statistical structure of natural stimuli, thereby optimizing coding. Recent evidence suggests that this is also the case for the vestibular system, which senses self-motion and in turn contributes to essential brain functions ranging from the most automatic reflexes to spatial perception and motor coordination. However, little is known about the statistics of self-motion stimuli actually experienced by freely moving animals in their natural environments. Accordingly, here we examined the natural self-motion signals experienced by mice and monkeys: two species commonly used to study vestibular neural coding. First, we found that probability distributions for all six dimensions of motion (three rotations, three translations) in both species deviated from normality due to long tails. Interestingly, the power spectra of natural rotational stimuli displayed similar structure for both species and were not well fitted by power laws. This result contrasts with reports that the natural spectra of other sensory modalities (i.e. vision, auditory and tactile) instead show a power-law relationship with frequency, which indicates scale invariance. Analysis of natural translational stimuli revealed important species differences as power spectra deviated from scale invariance for monkeys but not for mice. By comparing our results to previously published data for humans, we found the statistical structure of natural self-motion stimuli in monkeys and humans more closely resemble one another. Our results thus predict that, overall, neural coding strategies used by vestibular pathways to encode natural self-motion stimuli are fundamentally different in rodents and primates.

Integration of canal and otolith inputs by central vestibular neurons is subadditive for both active and passive self-motion: implication for perception.

Traditionally, the neural encoding of vestibular information is studied by applying either passive rotations or translations in isolation. However, natural vestibular stimuli are typically more complex. During everyday life, our self-motion is generally not restricted to one dimension, but rather comprises both rotational and translational motion that will simultaneously stimulate receptors in the semicircular canals and otoliths. In addition, natural self-motion is the result of self-generated and externally generated movements. However, to date, it remains unknown how information about rotational and translational components of self-motion is integrated by vestibular pathways during active and/or passive motion. Accordingly, here, we compared the responses of neurons at the first central stage of vestibular processing to rotation, translation, and combined motion. Recordings were made in alert macaques from neurons in the vestibular nuclei involved in postural control and self-motion perception. In response to passive stimulation, neurons did not combine canal and otolith afferent information linearly. Instead, inputs were subadditively integrated with a weighting that was frequency dependent. Although canal inputs were more heavily weighted at low frequencies, the weighting of otolith input increased with frequency. In response to active stimulation, neuronal modulation was significantly attenuated (∼ 70%) relative to passive stimulation for rotations and translations and even more profoundly attenuated for combined motion due to subadditive input integration. Together, these findings provide insights into neural computations underlying the integration of semicircular canal and otolith inputs required for accurate posture and motor control, as well as perceptual stability, during everyday life.

The increased sensitivity of irregular peripheral canal and otolith vestibular afferents optimizes their encoding of natural stimuli.

Efficient processing of incoming sensory input is essential for an organism's survival. A growing body of evidence suggests that sensory systems have developed coding strategies that are constrained by the statistics of the natural environment. Consequently, it is necessary to first characterize neural responses to natural stimuli to uncover the coding strategies used by a given sensory system. Here we report for the first time the statistics of vestibular rotational and translational stimuli experienced by rhesus monkeys during natural (e.g., walking, grooming) behaviors. We find that these stimuli can reach intensities as high as 1500 deg/s and 8 G. Recordings from afferents during naturalistic rotational and linear motion further revealed strongly nonlinear responses in the form of rectification and saturation, which could not be accurately predicted by traditional linear models of vestibular processing. Accordingly, we used linear-nonlinear cascade models and found that these could accurately predict responses to naturalistic stimuli. Finally, we tested whether the statistics of natural vestibular signals constrain the neural coding strategies used by peripheral afferents. We found that both irregular otolith and semicircular canal afferents, because of their higher sensitivities, were more optimized for processing natural vestibular stimuli as compared with their regular counterparts. Our results therefore provide the first evidence supporting the hypothesis that the neural coding strategies used by the vestibular system are matched to the statistics of natural stimuli.

Statistics of the vestibular input experienced during natural self-motion: implications for neural processing.

It is widely believed that sensory systems are optimized for processing stimuli occurring in the natural environment. However, it remains unknown whether this principle applies to the vestibular system, which contributes to essential brain functions ranging from the most automatic reflexes to spatial perception and motor coordination. Here we quantified, for the first time, the statistics of natural vestibular inputs experienced by freely moving human subjects during typical everyday activities. Although previous studies have found that the power spectra of natural signals across sensory modalities decay as a power law (i.e., as 1/f(α)), we found that this did not apply to natural vestibular stimuli. Instead, power decreased slowly at lower and more rapidly at higher frequencies for all motion dimensions. We further establish that this unique stimulus structure is the result of active motion as well as passive biomechanical filtering occurring before any neural processing. Notably, the transition frequency (i.e., frequency at which power starts to decrease rapidly) was lower when subjects passively experienced sensory stimulation than when they actively controlled stimulation through their own movement. In contrast to signals measured at the head, the spectral content of externally generated (i.e., passive) environmental motion did follow a power law. Specifically, transformations caused by both motor control and biomechanics shape the statistics of natural vestibular stimuli before neural processing. We suggest that the unique structure of natural vestibular stimuli will have important consequences on the neural coding strategies used by this essential sensory system to represent self-motion in everyday life.

Multimodal integration of self-motion cues in the vestibular system: active versus passive translations.

The ability to keep track of where we are going as we navigate through our environment requires knowledge of our ongoing location and orientation. In response to passively applied motion, the otolith organs of the vestibular system encode changes in the velocity and direction of linear self-motion (i.e., heading). When self-motion is voluntarily generated, proprioceptive and motor efference copy information is also available to contribute to the brain's internal representation of current heading direction and speed. However to date, how the brain integrates these extra-vestibular cues with otolith signals during active linear self-motion remains unknown. Here, to address this question, we compared the responses of macaque vestibular neurons during active and passive translations. Single-unit recordings were made from a subgroup of neurons at the first central stage of sensory processing in the vestibular pathways involved in postural control and the computation of self-motion perception. Neurons responded far less robustly to otolith stimulation during self-generated than passive head translations. Yet, the mechanism underlying the marked cancellation of otolith signals did not affect other characteristics of neuronal responses (i.e., baseline firing rate, tuning ratio, orientation of maximal sensitivity vector). Transiently applied perturbations during active motion further established that an otolith cancellation signal was only gated in conditions where proprioceptive sensory feedback matched the motor-based expectation. Together our results have important implications for understanding the brain's ability to ensure accurate postural and motor control, as well as perceptual stability, during active self-motion.

Strong correlations between sensitivity and variability give rise to constant discrimination thresholds across the otolith afferent population.

The vestibular system is vital for our sense of linear self-motion. At the earliest processing stages, the otolith afferents of the vestibular nerve encode linear motion. Their resting discharge regularity has long been known to span a wide range, suggesting an important role in sensory coding, yet to date, the question of how this regularity alters the coding of translational motion is not fully understood. Here, we recorded from single otolith afferents in macaque monkeys during linear motion along the preferred directional axis of each afferent over a wide range of frequencies (0.5-16 Hz) corresponding to physiologically relevant stimulation. We used signal-detection theory to directly measure neuronal thresholds and found that values for single afferents were substantially higher than those observed for human perception even when a Kaiser filter was used to provide an estimate of firing rate. Surprisingly, we further found that neuronal thresholds were independent of both stimulus frequency and resting discharge regularity. This was because increases in trial-to-trial variability were matched by increases in sensitivity such that their ratio remains constant: a coding strategy that markedly differs from that used by semicircular canal vestibular afferents to encode rotations. Finally, using Fisher information, we show that pooling the activities of multiple otolith afferents gives rise to neural thresholds comparable with those measured for perception. Together, our results strongly suggest that higher-order structures integrate inputs across afferent populations to provide our sense of linear motion and provide unexpected insight into the influence of variability on sensory encoding.

Neuronal detection thresholds during vestibular compensation: contributions of response variability and sensory substitution.

The vestibular system is responsible for processing self-motion, allowing normal subjects to discriminate the direction of rotational movements as slow as 1-2 deg s(-1). After unilateral vestibular injury patients' direction-discrimination thresholds worsen to ∼20 deg s(-1), and despite some improvement thresholds remain substantially elevated following compensation. To date, however, the underlying neural mechanisms of this recovery have not been addressed. Here, we recorded from first-order central neurons in the macaque monkey that provide vestibular information to higher brain areas for self-motion perception. Immediately following unilateral labyrinthectomy, neuronal detection thresholds increased by more than two-fold (from 14 to 30 deg s(-1)). While thresholds showed slight improvement by week 3 (25 deg s(-1)), they never recovered to control values - a trend mirroring the time course of perceptual thresholds in patients. We further discovered that changes in neuronal response variability paralleled changes in sensitivity for vestibular stimulation during compensation, thereby causing detection thresholds to remain elevated over time. However, we found that in a subset of neurons, the emergence of neck proprioceptive responses combined with residual vestibular modulation during head-on-body motion led to better neuronal detection thresholds. Taken together, our results emphasize that increases in response variability to vestibular inputs ultimately constrain neural thresholds and provide evidence that sensory substitution with extravestibular (i.e. proprioceptive) inputs at the first central stage of vestibular processing is a neural substrate for improvements in self-motion perception following vestibular loss. Thus, our results provide a neural correlate for the patient benefits provided by rehabilitative strategies that take advantage of the convergence of these multisensory cues.

Context-independent encoding of passive and active self-motion in vestibular afferent fibers during locomotion in primates.

The vestibular system detects head motion to coordinate vital reflexes and provide our sense of balance and spatial orientation. A long-standing hypothesis has been that projections from the central vestibular system back to the vestibular sensory organs (i.e., the efferent vestibular system) mediate adaptive sensory coding during voluntary locomotion. However, direct proof for this idea has been lacking. Here we recorded from individual semicircular canal and otolith afferents during walking and running in monkeys. Using a combination of mathematical modeling and nonlinear analysis, we show that afferent encoding is actually identical across passive and active conditions, irrespective of context. Thus, taken together our results are instead consistent with the view that the vestibular periphery relays robust information to the brain during primate locomotion, suggesting that context-dependent modulation instead occurs centrally to ensure that coding is consistent with behavioral goals during locomotion.

Sensory adaptation mediates efficient and unambiguous encoding of natural stimuli by vestibular thalamocortical pathways.

Sensory systems must continuously adapt to optimally encode stimuli encountered within the natural environment. The prevailing view is that such optimal coding comes at the cost of increased ambiguity, yet to date, prior studies have focused on artificial stimuli. Accordingly, here we investigated whether such a trade-off between optimality and ambiguity exists in the encoding of natural stimuli in the vestibular system. We recorded vestibular nuclei and their target vestibular thalamocortical neurons during naturalistic and artificial self-motion stimulation. Surprisingly, we found no trade-off between optimality and ambiguity. Using computational methods, we demonstrate that thalamocortical neural adaptation in the form of contrast gain control actually reduces coding ambiguity without compromising the optimality of coding under naturalistic but not artificial stimulation. Thus, taken together, our results challenge the common wisdom that adaptation leads to ambiguity and instead suggest an essential role in underlying unambiguous optimized encoding of natural stimuli.

The oculogyral illusion: retinal and oculomotor factors.

Subjects in a dark chamber exposed to angular acceleration while viewing a head-fixed target experience motion and displacement of the target relative to their body. Competing explanations of this phenomenon, known as the oculogyral illusion, have attributed it to the suppression of the vestibulo-ocular reflex (VOR) or to retinal slip. In the dark, the VOR evokes compensatory eye movements in the direction opposite to body acceleration. A head-fixed visual target will tend to suppress these eye movements. The VOR suppression hypothesis attributes the oculogyral illusion to the signals that prevent reflexive deviation of the eyes from the target thus resulting in apparent target displacement in the direction of acceleration. The retinal slip hypothesis attributes the illusion to inadequate fixation of the target with the eyes being involuntarily deviated in the direction opposite acceleration, the retinal slip being interpreted as target displacement in the direction of acceleration. Another possibility is that the illusion could arise from a change in the representation of the perceived head midline. To evaluate these three alternative hypotheses, we tested 8 subjects at 4 acceleration rates (2, 10, 20, 30°/s²) in each of three conditions: (a) fixate and point to a target light; (b) fixate to the target light and point to the head midline; (c) look straight ahead in the dark. The displacement magnitude of the oculogyral illusion was least at 2°/s² ≈ 2° and was ≈10° at the other acceleration rates. The presence of the target light significantly attenuated eye movements relative to the dark condition, but eye movements were still present at the 10, 20, and 30°/s² accelerations. The eye velocity profiles in the dark at different acceleration rates did not show a one-to-one inverse mapping to the magnitude of the oculogyral illusion at those rates. The perceived head midline was not significantly displaced at any of the acceleration rates. The oculogyral illusion thus has at least two contributing factors: the suppression of nystagmus at low acceleration rates and at higher acceleration rates, a partial suppression coupled with an integration of the drift of the eyes with respect to the fixation target.

Internal models of self-motion: computations that suppress vestibular reafference in early vestibular processing.

In everyday life, vestibular sensors are activated by both self-generated and externally applied head movements. The ability to distinguish inputs that are a consequence of our own actions (i.e., active motion) from those that result from changes in the external world (i.e., passive or unexpected motion) is essential for perceptual stability and accurate motor control. Recent work has made progress toward understanding how the brain distinguishes between these two kinds of sensory inputs. We have performed a series of experiments in which single-unit recordings were made from vestibular afferents and central neurons in alert macaque monkeys during rotation and translation. Vestibular afferents showed no differences in firing variability or sensitivity during active movements when compared to passive movements. In contrast, the analyses of neuronal firing rates revealed that neurons at the first central stage of vestibular processing (i.e., in the vestibular nuclei) were effectively less sensitive to active motion. Notably, however, this ability to distinguish between active and passive motion was not a general feature of early central processing, but rather was a characteristic of a distinct group of neurons known to contribute to postural control and spatial orientation. Our most recent studies have addressed how vestibular and proprioceptive inputs are integrated in the vestibular cerebellum, a region likely to be involved in generating an internal model of self-motion. We propose that this multimodal integration within the vestibular cerebellum is required for eliminating self-generated vestibular information from the subsequent computation of orientation and posture control at the first central stage of processing.

Challenges to the Vestibular System in Space: How the Brain Responds and Adapts to Microgravity.

In the next century, flying civilians to space or humans to Mars will no longer be a subject of science fiction. The altered gravitational environment experienced during space flight, as well as that experienced following landing, results in impaired perceptual and motor performance-particularly in the first days of the new environmental challenge. Notably, the absence of gravity unloads the vestibular otolith organs such that they are no longer stimulated as they would be on earth. Understanding how the brain responds initially and then adapts to altered sensory input has important implications for understanding the inherent abilities as well as limitations of human performance. Space-based experiments have shown that altered gravity causes structural and functional changes at multiple stages of vestibular processing, spanning from the hair cells of its sensory organs to the Purkinje cells of the vestibular cerebellum. Furthermore, ground-based experiments have established the adaptive capacity of vestibular pathways and neural mechanism that likely underlie this adaptation. We review these studies and suggest that the brain likely uses two key strategies to adapt to changes in gravity: (i) the updating of a cerebellum-based internal model of the sensory consequences of gravity; and (ii) the re-weighting of extra-vestibular information as the vestibular system becomes less (i.e., entering microgravity) and then again more reliable (i.e., return to earth).

Neural variability determines coding strategies for natural self-motion in macaque monkeys.

We have previously reported that central neurons mediating vestibulo-spinal reflexes and self-motion perception optimally encode natural self-motion (Mitchell et al., 2018). Importantly however, the vestibular nuclei also comprise other neuronal classes that mediate essential functions such as the vestibulo-ocular reflex (VOR) and its adaptation. Here we show that heterogeneities in resting discharge variability mediate a trade-off between faithful encoding and optimal coding via temporal whitening. Specifically, neurons displaying lower variability did not whiten naturalistic self-motion but instead faithfully represented the stimulus' detailed time course, while neurons displaying higher variability displayed temporal whitening. Using a well-established model of VOR pathways, we demonstrate that faithful stimulus encoding is necessary to generate the compensatory eye movements found experimentally during naturalistic self-motion. Our findings suggest a novel functional role for variability toward establishing different coding strategies: (1) faithful stimulus encoding for generating the VOR; (2) optimized coding via temporal whitening for other vestibular functions.

Learning to use vestibular sense for spatial updating is context dependent.

As we move, perceptual stability is crucial to successfully interact with our environment. Notably, the brain must update the locations of objects in space using extra-retinal signals. The vestibular system is a strong candidate as a source of information for spatial updating as it senses head motion. The ability to use this cue is not innate but must be learned. To date, the mechanisms of vestibular spatial updating generalization are unknown or at least controversial. In this paper we examine generalization patterns within and between different conditions of vestibular spatial updating. Participants were asked to update the position of a remembered target following (offline) or during (online) passive body rotation. After being trained on a single spatial target position within a given task, we tested generalization of performance for different spatial targets and an unpracticed spatial updating task. The results demonstrated different patterns of generalization across the workspace depending on the task. Further, no transfer was observed from the practiced to the unpracticed task. We found that the type of mechanism involved during learning governs generalization. These findings provide new knowledge about how the brain uses vestibular information to preserve its spatial updating ability.

Coding strategies in the otolith system differ for translational head motion vs. static orientation relative to gravity.

The detection of gravito-inertial forces by the otolith system is essential for our sense of balance and accurate perception. To date, however, how this system encodes the self-motion stimuli that are experienced during everyday activities remains unknown. Here, we addressed this fundamental question directly by recording from single otolith afferents in monkeys during naturalistic translational self-motion and changes in static head orientation. Otolith afferents with higher intrinsic variability transmitted more information overall about translational self-motion than their regular counterparts, owing to stronger nonlinearities that enabled precise spike timing including phase locking. By contrast, more regular afferents better discriminated between different static head orientations relative to gravity. Using computational methods, we further demonstrated that coupled increases in intrinsic variability and sensitivity accounted for the observed functional differences between afferent classes. Together, our results indicate that irregular and regular otolith afferents use different strategies to encode naturalistic self-motion and static head orientation relative to gravity.

Cerebellar Prediction of the Dynamic Sensory Consequences of Gravity.

As we go about our everyday activities, our brain computes accurate estimates of both our motion relative to the world and our orientation relative to gravity. However, how the brain then accounts for gravity as we actively move and interact with our environment is not yet known. Here, we provide evidence that, although during passive movements, individual cerebellar output neurons encode representations of head motion and orientation relative to gravity, these gravity-driven responses are cancelled when head movement is a consequence of voluntary generated movement. In contrast, the gravity-driven responses of primary otolith and semicircular canal afferents remain intact during both active and passive self-motion, indicating the attenuated responses of central neurons are not inherited from afferent inputs. Taken together, our results are consistent with the view that the cerebellum builds a dynamic prediction (e.g., internal model) of the sensory consequences of gravity during active self-motion, which in turn enables the preferential encoding of unexpected motion to ensure postural and perceptual stability.

Neuronal variability and tuning are balanced to optimize naturalistic self-motion coding in primate vestibular pathways.

It is commonly assumed that the brain's neural coding strategies are adapted to the statistics of natural stimuli. Specifically, to maximize information transmission, a sensory neuron's tuning function should effectively oppose the decaying stimulus spectral power, such that the neural response is temporally decorrelated (i.e. 'whitened'). However, theory predicts that the structure of neuronal variability also plays an essential role in determining how coding is optimized. Here, we provide experimental evidence supporting this view by recording from neurons in early vestibular pathways during naturalistic self-motion. We found that central vestibular neurons displayed temporally whitened responses that could not be explained by their tuning alone. Rather, computational modeling and analysis revealed that neuronal variability and tuning were matched to effectively complement natural stimulus statistics, thereby achieving temporal decorrelation and optimizing information transmission. Taken together, our findings reveal a novel strategy by which neural variability contributes to optimized processing of naturalistic stimuli.